FCE 24517-resistant MCF-7 human breast cancer cell line: selection and characterization

We have developed a stable line of the human breast carcinoma cell line MCF -7 by in vitro continuous exposure to increasing concentrations of the anti tumoral alkylating agent FCE 24517 (tallimustine). The selected line, MCF-7 / 24517,, was resistant to the selecting agent (RI=10) and to a lesser degr ee to melphalan, MEN 10710 (a related dystamycin analog), doxorubicin and e toposide, but not to m-AMSA. MCF-7/24517(1) cells did not express the multi drug-resistant phenotype, evaluated in terms of mRNA for mdr-1 and gp170 gl ycoprotein. A significant, albeit modest, increase in the cellular content of glutathione was measured and therefore other resistance mechanism(s) sho uld be operative. We conclude that the MCF-7/24517(1) line is a valuable mo del to investigate the mechanisms of resistance of FCE 24517 and its deriva tives. [(C) 1999 Lippincott Williams & Wilkins.].